Avian reticuloendotheliosis virus (REV-T) is a replication-defective acute leukemia virus that transforms immature lymphocytes. REV-T stocks contain a replication-competent nontransforming helper virus (reticuloendotheliosis-associated virus: REV-A) which is present in 1000-fold excess. REV-A induces a suppressor cell population in the spleens of infected birds which can be detected within three days after virus infection. The suppressor cells prevent the proliferation of thymus-derived lymphocytes by a contact-mediated mechanism. We intend to define the mechanism by which REV-A induces this suppressor cell population. Replicating REV-A as well as other genetically related reticuloendotheliosis viruses induce this suppressor cell population suggesting that the induction of suppressor cells may be mediated by a viral precursor polypeptide. REV-T nonvirus-producing transformed cells which do not contain viral precursor polypeptides but express a surface protein related to REV-A also induce suppressor cells. REV-A precursor polypeptides sharing sequences with the tumor cell antigen will be tested for their ability to induce suppressor cells and characterize the interaction between suppressor cells and immunoresponsive cells. Impairment of the cellular immune response is a general feature of the helper viruses of all known avian acute leukemia viruses. A number of experimental approaches will be employed to define whether helper virus-induced immunosuppression plays a significant role in the pathogenesis of viral-induced leukemia. The role of the helper virus-induced immunosuppression on the tumorigenicity and invasive properties of REV-T-transformed cells will be evaluated.